Transplanting kidneys from donors with small renal masses - a strategy to expand the donor pool.

INTRODUCTION: Renal transplantation is the optimal treatment for end-stage renal disease, but organ demand continues to outstrip supply. The transplantation of kidneys from donors with small renal masses (SRMs) represents a potential avenue to expand the donor pool. We reviewed all published cases of transplants from donors with SRMs and we present followup data, best practices, and outline an actionable series of steps to guide the implementation of such transplants at individual centers. METHODS: A detailed literature search of the MEDLINE/PubMed and SCOPUS databases was performed. Thirty unique data sets met inclusion criteria and described the transplantation of tumor-ectomized kidneys; nine data sets described the transplantation of contralateral kidneys from donors with SRMs. RESULTS: A total of 147 tumorectomized kidneys have been transplanted. Pathology revealed 120 to be renal cell carcinomas (RCCs), of which 116 were stage T1a (0.3-4 cm). The mean followup time was 44.2 months (1-200). A single suspected tumor recurrence occurred in one patient nine years post-transplantation and it was managed with active surveillance. Twenty-seven kidneys have been transplanted from deceased donors with contralateral renal masses. Pathology revealed 25 to be RCCs, of which 19 were confirmed to be stage T1 (<7 cm). The mean followup time was 46.7 months (0.5-155). One recipient developed an RCC and underwent curative allograft nephrectomy. CONCLUSIONS: Careful use of kidneys from donors with SRMs is feasible and safe, with an overall recurrence rate of less than 1.5%. The use of such kidneys could help alleviate the organ shortage crisis.

Characteristics and Outcomes of Exit Sites of Buried Peritoneal Dialysis Catheters: A Cohort Study.

Buried peritoneal dialysis (PD) catheters are placed months before dialysis is needed and the exit site is created when the catheter is dissected out at the initiation of dialysis. In contrast, the exit site of an unburied catheter is created by the surgeon at the time of insertion. We reviewed all patients who initiated PD at our center over a 2-year period. At each clinic visit, exit sites were subjectively classified into standard predefined groups. Outcomes of interest were the frequency of perfect exit sites at 2, 6, and 12 months and rate of exit-site infections (ESIs) at 90 days. One hundred and seventy-seven patients initiated PD during the period of interest, and 169, 157, and 144 remained on PD at 2, 6, and 12 months, respectively. Ninety-three patients had buried catheters, and 76 patients had unburied catheters. Both groups had similar frequency of perfect appearance of exit sites at 2, 6, and 12 months (37/93 vs 41/76 at 2 months; 54/87 vs 43/70 at 6 months; 50/ 81 vs 35/ 63 at 12 months in buried and unburied groups, respectively). More patients with buried catheters had ESIs in the first 3 months (7/93 vs 1/76, p = 0.059). We conclude that exit sites of buried PD catheters do not differ qualitatively from those of unburied catheters. The trend towards more ESIs with buried catheters suggests that there may be clinical consequences of the tissue trauma at time of exteriorization.

Drivers and mechanisms of tree mortality in moist tropical forests.

Tree mortality rates appear to be increasing in moist tropical forests (MTFs) with significant carbon cycle consequences. Here, we review the state of knowledge regarding MTF tree mortality, create a conceptual framework with testable hypotheses regarding the drivers, mechanisms and interactions that may underlie increasing MTF mortality rates, and identify the next steps for improved understanding and reduced prediction. Increasing mortality rates are associated with rising temperature and vapor pressure deficit, liana abundance, drought, wind events, fire and, possibly, CO2 fertilization-induced increases in stand thinning or acceleration of trees reaching larger, more vulnerable heights. The majority of these mortality drivers may kill trees in part through carbon starvation and hydraulic failure. The relative importance of each driver is unknown. High species diversity may buffer MTFs against large-scale mortality events, but recent and expected trends in mortality drivers give reason for concern regarding increasing mortality within MTFs. Models of tropical tree mortality are advancing the representation of hydraulics, carbon and demography, but require more empirical knowledge regarding the most common drivers and their subsequent mechanisms. We outline critical datasets and model developments required to test hypotheses regarding the underlying causes of increasing MTF mortality rates, and improve prediction of future mortality under climate change.

Preoperative Cylex assay predicts rejection risk in patients with kidney transplant.

INTRODUCTION AND OBJECTIVES: The ImmuKnow assay measures cell-mediated immunity by quantifying ATP release from CD4+ T-cells in peripheral blood. Herein, we hypothesized that this assay could predict complications associated with over-/under-immunosuppression in patients with kidney transplant (KT). METHODS: Sixty-seven patients undergoing KT were recruited prospectively and had ATP levels measured preoperatively, and at specified intervals over two months. Clinicians were blinded to ATP levels. Clinical events including rejection and infection/cancer were documented with a median follow-up of 21 months. Parameters including absolute ATP levels and changes in ATP patterns (slopes, delta) were analyzed. Association between ATP parameters and clinical outcomes was compared using the likelihood-ratio test and Kaplan-Meier curves. RESULTS: Absolute ATP values postoperatively had poor predictive value with regard to rejection or infection/malignancy. As well, changes in ATP values were poorly associated with complications. Importantly, patients with pre-transplant ATP values <300 ng/mL had significantly less rejection episodes vs. those with ATP values >300 ng/mL (p < 0.0001). CONCLUSIONS: For the first time, we have evidence that a preoperative ImmuKnow level can stratify patients with KT into low/high risk groups for rejection. Future studies used to assess the utility of this assay to design individualized immunosuppressive regimens are required.

Should peritoneal dialysis catheters be removed at the time of kidney transplantation?

BACKGROUND: : Delayed graft function (DGF) following transplantation necessitates support in the form of hemodialyis (HD) or peritoneal dialysis (PD). However, post-transplant PD-related complication and failure rates are unknown. METHODS: : We studies patients who were on PD at the time of kidney transplantation over a 4-year period at two separate institutions. RESULTS: : Of the 137 PD patients, 19 had their catheters removed at the time of transplant. Of the remaining 118 patients, 89% had immediate graft function. PD-related complications in this group included peritonitis (n=5), catheter-related infections (n=2) and emergency laparotomy (n=1). Of the 15 patients requiring post-transplant PD, 33% developed peritonitis and 20% had fluid-leaks necessitating HD. Overall, leaving a PD catheter in situ post- transplantation is associated with 7% rate of peritonitis versus 0% if removed (p < 0.05). CONCLUSIONS: : PD catheter removal should be considered at the time of renal transplantation, as postoperative PD-related failure/complication rates are high.

Extracapsular versus intracapsular allograft nephrectomy: impact on allosensitization and surgical outcomes.

INTRODUCTION: Our objective was to compare the impact of extra-capsular (ECAN) versus intracapsular allograft nephrectomy (ICAN) on allosensitization and surgical outcomes. METHODS: Between 1990 and 2004, 96 allograft nephrectomies were performed at our institution. Of these, 29 procedures were performed within 1 month of the transplant and were therefore omitted from analysis. Overall, the results of 44 ECAN and 23 ICAN were reviewed. RESULTS: The mean operative times were 110.9 versus 130.4 min for ICAN versus ECAN (p = 0.02) and the estimated blood loss was 226 mL for ICAN versus 483 mL for ECAN (p = 0.004). Intraoperative and postoperative complications were low using either technique and differences were not statistically significant. Overall, the preoperative to postoperative change in the percentage of panel reactive antibody was +2.1% for ICAN versus +1.2% for ECAN (NS) at 3 to 12 months postoperatively, respectively (NS). The percentage of patients relisted was 33.3% versus 54.3% (NS), and the percentage of patients re-transplanted once relisted was also very similar: 63.2% for ECAN versus 66.7% for ICAN (NS), after a mean follow-up of 4.5 and 8.4 years, respectively. CONCLUSIONS: ICAN can be performed with shorter operative times and less blood loss versus the extracapsular approach. As well, this operative approach does not appear to affect allosensitization and the ability to re-transplant patients.

Robot-assisted pyeloplasty: follow-up of first Canadian experience with comparison of outcomes between experienced and trainee surgeons.

BACKGROUND AND PURPOSE: Robot-assisted pyeloplasty (RAP) has been established recently as an option in the management of ureteropelvic junction obstruction (UPJO). We present the first Canadian experience with RAP with respect to operative results and outcomes. We compare the surgical outcomes between experienced and trainee surgeons, with respect to operating room times and success rates. PATIENTS AND METHODS: Eighty-eight patients underwent transperitoneal RAP for UPJO using the da Vinci robotic platform. Two surgeons performed Anderson-Hynes dismembered pyeloplasty in 85 cases and YV-plasty in 5 cases. Five patients had RAP for secondary UPJO after failure of other treatments. Diuretic renography was performed at 6 weeks, and 6, 12, 18, 24, and 36 months postpyeloplasty. The mean follow-up was 14.1 ± 8.5 months. RESULTS: The mean operative time was 167.7 ± 43.2 minutes, and the mean anastomotic time was 41.9 ± 14.1 minutes. The mean operative duration significantly decreased with time (P < 0.05). Ten patients needed simultaneous nephroscopic stone management via the pyelotomy incision. The mean blood loss was 56.6 ± 55.4 mL, and the mean hospital stay was 2.5 ± 0.5 days. There were five major postoperative (stent migration, urinoma) and three minor complications that were associated with the RAP procedures. Postoperative renal scintigraphy demonstrated only four cases with persistent obstruction. Eighty-three (94.3%) patients experienced improvement of symptoms whereas 5 continued to be symptomatic. Two patients needed secondary procedures to relieve persisting obstruction. There were no statistical differences in outcomes between the experienced surgeons and trainees (P = 0.28). CONCLUSIONS: In the first large case series of RAP from Canada, we demonstrate that RAP can be performed with relatively short operative times and is safe and effective, achieving similar long-term results with standard open repair. We show that robot-assisted surgery can be safely transitioned to surgical trainees. With its cost and availability, its role in the Canadian system needs further study.

Outcome of third renal allograft retransplants versus primary transplants from paired donors.

BACKGROUND: Third kidney retransplants have technical and immunologic hurdles that may preclude success, which is of particular importance in the contemporary context of discrepancy between organ supply and demand. METHODS: The outcomes of third renal transplant recipients (TRTR) were compared with those receiving a first transplant from paired donor kidneys to assess transplant success and complication rates. The Ontario-based Trillium Gift of Life Network database was used to identify deceased donors (n=28) who donated one kidney to a TRTR and the mate kidney to a primary renal transplant recipient (PRTR) from June 1977 to August 2006. RESULTS: As anticipated, TRTR were sensitized versus PRTR based on % panel reactive antibodies (24%+/-34% vs. 7%+/-14%, P=0.03). Delayed graft function (46% vs. 22%, P=0.05) and biopsy-proven rejection episodes (50% vs. 29%, P=0.01) occurred more frequently with TRTR despite greater frequency of induction therapy (74% vs. 35%, P=0.004). However, 1- and 5-year patient survival were similar at 93%, 83% and 96%, 87% for TRTR and PRTR, respectively. Accordingly, 1- and 5-year allograft survival censored for mortality, were comparable at 78%, 66% and 78%, 75%. Renal function was similar in both groups. Bacterial infections (43% vs. 18%, P=0.001) and wound problems (28% vs. 11%, P=0.09) were the only postoperative complications to occur more frequently in the TRTR. CONCLUSION: We conclude that third renal transplantation should not be discouraged based on functional outcomes alone.

Immunosuppression without calcineurin inhibition: optimization of renal function in expanded criteria donor renal transplantation.

INTRODUCTION: To assess the efficacy of calcineurin inhibitor (CNI)-free immunosuppression vs. calcineurin-based immunosuppression in patients receiving expanded criteria donor (ECD) kidneys. PATIENT AND METHODS: Thirteen recipients of ECD kidneys were enrolled in this pilot study and treated with induction therapy and maintained on sirolimus, mycophenolate mofetil (MMF) and prednisone. A contemporaneous control group was randomly selected comprised of 13 recipients of ECD kidneys who had been maintained on CNI plus MMF and prednisone. RESULTS: For the study group vs. the control group, two-yr graft survival was 92.3% vs. 84.6% (p = NS), two-yr patient survival was 100% vs. 92.3% (p = NS) and the acute rejection rates were 23% vs. 31% (p = NS), respectively. Renal function was significantly better in the study group compared with control up to the six-month mark, after which, it remained numerically but not statistically significant. Complications were more common in the study group, but serious adverse events requiring discontinuation were rare. CONCLUSION: This pilot study demonstrates that CNI-free regimens can be safely implemented in patients receiving ECD kidneys with excellent two-yr patient and graft survival and good renal allograft function. Longer follow-up in larger randomized controlled trials are necessary to establish these findings.

Retrograde stenting of transplant ureters using a ureteral access sheath.

Changing chronic ureteral stents in patients with kidney transplants may be technically difficult because of the site of ureterocystostomy. The technique described simplifies this procedure.

Posterior urethral valves in Eastern Ontario - a 30 year perspective.

INTRODUCTION: Posterior urethral valves (PUV) are the most common cause of male pediatric obstructive uropathy. Recent advancements in antenatal ultrasound and endoscopy have altered the presentation and management of PUV. Herein we describe the presentation, management and outcome of PUV patients in Eastern Ontario/Western Quebec over the last 3 decades. A comparison analysis of those cases identified pre and post widespread utilization of antenatal ultrasound diagnosis was performed to discern the clinical evolution of PUV with respect to long-term outcome. METHODS: Retrospective systematic chart review of all PUV cases diagnosed and treated at the Children's Hospital of Eastern Ontario over the last 3 decades. Charts were reviewed for initial presentation, method of diagnosis, radiological and clinical findings at diagnosis, initial management, and long-term clinical outcome. The evolution of PUV was interpreted by dividing the cohort into two groups chronologically delineated by the first case detected by antenatal ultrasound in the mid-1980s. These pre- and post- antenatal ultrasound eras were compared with respect to the parameters outlined above. RESULTS: Fifty-three cases were reviewed - 21 prior to widespread antenatal ultrasound screening in the mid-1980s and 32 after. There were 13/53 cases (32%) discovered by prenatal ultrasound evidence of hydronephrosis, none prior to 1985. VCUG confirmed the diagnosis in all cases. Mean age at presentation in the remaining post-natally diagnosed patients was 33 months. Of the cases diagnosed post-natally, ultrasound investigation complemented VCUG findings in 19/40 cases (47%), whereas IVP was utilized in 14/40 (35%). IVP has not been utilized for this purpose since 1987. Overall, 26/53 cases (49%) had documented VUR - 16/26 (62%) bilateral; 42/53 (79%) had hydronephrosis on ultrasound - 37/42 (88%) bilateral; 26/53 (49%) had radiological evidence of renal parenchymal damage at diagnosis; 41/53 (77%) cases had a thickened bladder wall on ultrasound at diagnosis, and 23/53 (43%) had at least one bladder diverticulum. Techniques of initial management comprised: valve ablation 32/53, vesicostomy 11/53, and high diversion 10/53. Clinically significant bladder dysfunction was found in 31% of cases, ranging from bladder instability to myogenic failure. Globally impaired renal function, as determined by significantly elevated serum creatinine levels, reduced GFR, or both, was found in 12/53 (23%). 6/53 (11%) progressed to ESRD, of which 4 received transplants. Two patients died - one from complications related to renal failure. Of the six cases of myogenic bladder failure identified, three (50%) had concurrently significant renal impairment. Average length of follow-up was 8.3 years, varying between 1 month and 18 years. CONCLUSIONS: The presentation of PUV is variable, and currently antenatal detection is the most common mode. Despite this, it still does not make up the majority of diagnoses. Complete radiological work up should include abdominal and pelvic U/S in conjunction with VCUG. Concurrent VUR in 50% of boys mandates suppressive antibiotic use. Primary valve ablation remains the gold standard for treatment of PUV, with vesicostomy reserved for selected cases. Long-term bladder and renal dysfunction is common in this population, and mandates long-term urological and nephrological follow-up.